Steroid hormones have been implicated in playing a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes or hormones involved in androgen regulatory pathway are proposed to influence an individual's risk for developing prostate cancer. Such polymorphic genes that exist within the androgen biosynthesis and/or metabolism pathway and which have been suggested to be associated with prostate cancer risk include 5α-reductase type 2 and the cytochrome P450 17α-hydroxylase (CYP17). CYP17 encodes an enzyme with both 17α-hydroxylase and 17,20-lyase activities, the rate-limiting steps in androgen biosynthesis.
The mechanisms involved in the transport of steroid hormones through biological membranes, and their accumulation within target cells, are still not completely understood. The lipophilic nature of steroid hormones has led to the concept that the cell membrane plays a passive role in the transport of steroids. However, several members of different uptake transporter families have been localized to this membrane domain. One large family of uptake transporters is the OATP (organic anion transporting polypeptides) family of solute carriers. Endogenous substances, such as bile acids, steroids, thyroid hormones, and prostaglandins are substrates of members of the OATP family. Encoding members of this family are expressed in human hepatocytes: SLCO1B1 encoding OATP1B1, SLCO1B3 encoding OATP1B3, and SLCO2B1 encoding OATP2B1. OATP1B3, located in the basolateral membrane of human hepatocytes, is involved in the hepatocellular uptake of endogenous and exogenous organic anions. Endogenous substrates for OATP1B3 include 17-glucuronosyl estradiol, dehydroepiandrosterone-3-sulfate (DHEAS), bile acids (e.g., cholyltaurine and cholylglycine), and peptide hormones (e.g., cholecystokinin-8 (CCK-8)). DHEAS affects the developing prostate cancer.
Since membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival. While a polymorphism in SLCO1B3 has been associated with increased prostate cancer risk, the relationship of the SLCO1B3 polymorphism and clinical outcome remains unclear. Thus, there is a need in the art to assess polymorphism in SLCO1B3 and prostate cancer clinical outcome and for prostate cancer susceptibility.